Mithramycin oxime derivatives having increased selectivity and anti-cancer activity

Abstract

Compounds described herein are mithramycin (MTM) oxide (OX) derivatives. These compounds are useful for treatment of cancers and neuro-diseases.

What is claimed is: 
     
         1 . A compound having the following formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein R is selected from the group consisting of substituted or unsubstituted amino acid, amino acid dipeptide, acyl-amino acid, and acyl-amino acid dipeptide. 
     
     
         2 . The compound of  claim 1 , wherein R is acyl-amino acid or acyl-amino acid dipeptide. 
     
     
         3 . The compound of  claim 1 , wherein R is substituted acyl-amino acid or acyl-amino acid dipeptide. 
     
     
         4 . The compound of  claim 1 , wherein R is a substituted amino acid, amino acid dipeptide, acyl-amino acid, and acyl-amino acid dipeptide, wherein the substitution is a quinolone, a benzothizole, a phenyl, a pyridine, or an indol group. 
     
     
         5 . The compound of  claim 1 , wherein R is an amino acid or amino acid dipeptide group, or a substituted amino acid or amino acid dipeptide group. 
     
     
         6 . A method of treating Ewing sarcoma, prostate cancer, colon cancer, lung cancer, leukemia, and/or lymphoma in a patient in need thereof, the method comprising administering to the patient a therapeutically effective amount of the compound of  claim 1 . 
     
     
         7 . The method of  claim 6 , wherein the method comprises treating Ewing sarcoma. 
     
     
         8 . The method of  claim 6 , wherein the method comprises treating prostate cancer. 
     
     
         9 . The method of  claim 6 , wherein the method comprises treating colon cancer. 
     
     
         10 . The method of  claim 6 , wherein the method comprises treating lung cancer. 
     
     
         11 . The method of  claim 6 , wherein the method comprises treating leukemia or lymphoma. 
     
     
         12 . A method for selectively inhibiting EWS-FLI1 transcription factors in a patient in need thereof, including administering to the patient a therapeutically effective amount of the compound of  claim 1 .